Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT01254630 | A Study to Evaluate the Safety and Efficacy of Inactivated Varicella-zoster Vaccine (VZV) as a Preventative Treatment for Herpes Zoster (HZ) and HZ-related Complications in Adult Participants With Solid Tumor or Hematologic Malignancy (V212-011) | PHASE3 | COMPLETED | 5,305 | — | — | Jun 24, 2011 | Apr 11, 2017 | Sep 30, 2019 | - | — |
| NCT01229267 | A Study to Evaluate the Safety and Efficacy of Inactivated Varicella-zoster Vaccine (VZV) as a Preventative Treatment for Herpes Zoster (HZ) and HZ-related Complications in Participants Undergoing Hematopoietic Cell Transplants (HCTs) (V212-001) | PHASE3 | COMPLETED | 1,257 | — | — | Nov 30, 2010 | Dec 23, 2015 | Sep 30, 2019 | - | — |
| NCT01527383 | A Study to Evaluate the Safety and Immunogenicity of Inactivated Varicella Zoster Virus (VZV) Vaccine in Adults With Autoimmune Disease (V212-009) | PHASE2 | COMPLETED | 354 | — | — | Feb 21, 2012 | Feb 26, 2013 | Jan 14, 2019 | - | — |
| NCT01460719 | A Study to Evaluate the Safety and Immunogenicity of Inactivated Varicella-Zoster Virus (VZV) Vaccine in Adults With Hematologic Malignancies (HM) Receiving Treatment With Anti-Cluster of Differentiation (CD) 20 Monoclonal Antibodies (V212-013) | PHASE1 | COMPLETED | 80 | — | — | Jan 24, 2012 | Sep 25, 2012 | Mar 11, 2019 | - | — |
| NCT00886613 | A Study to Evaluate Immunity to Varicella Zoster Virus After Immunization With V212 Vaccine or Zostavax (V212-003) | PHASE1 | COMPLETED | 120 | — | — | Mar 1, 2009 | Dec 1, 2009 | Oct 6, 2015 | - | — |
| NCT00696709 | A Study to Test the Safety and Antibody Response of V212 in Healthy Adults (V212-004)(COMPLETED) | PHASE1 | COMPLETED | 290 | — | — | Dec 12, 2008 | Nov 16, 2009 | Nov 8, 2019 | - | — |
| NCT00535236 | A Study of an Investigational V212/Heat-Treated Varicella-Zoster Virus (VZV) Vaccine in Immunocompromised Adults (V212-002) | PHASE1 | COMPLETED | 341 | — | — | Nov 2, 2007 | Jan 26, 2010 | May 20, 2019 | - | — |
Clinical criteria for suspected HZ cases were the development of a papular or vesicular rash with a dermatomal or generalized distribution, or in the absence of a rash, clinical suspicion of VZV infection with or without the detection of VZV in diagnostic specimens from blood, cerebrospinal fluid, lung, liver, or other organ. All suspected cases of HZ were subjected to adjudication by the Clinical Adjudication Committee (CAC). Case confirmation was based on skin lesion polymerase chain reaction, if available, or by adjudication of the clinical case description by the CAC, conducted according to the CAC Standard Operations Procedure.
An adverse event (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the sponsor's product, whether or not considered related to the use of the product. A serious adverse event (SAE) is an AE that results in death, is life threatening, results in a persistent or significant disability or incapacity, results in or prolongs an existing hospitalization, is a congenital anomaly or birth defect, is a cancer, is an overdose, or is another important medical event.
Serum samples were tested for antibody response using a gpELISA. The GMFR is response at approximately 28 days postdose 4 / response predose on Day 1.
Serum samples were tested for activity using a VZV ELISPOT assay. The assay detects IFN-γ-secreting, VZV-specific cells from peripheral blood mononuclear cells (PBMCs). The unit of measure of the assay is ELISPOT cell count / 10\^6 PBMCs, and is expressed as geometric mean count (GMC). The GMFR is GMC at \~28 days after Vaccination 4 / GMC predose on Day 1.
A serious adverse event (SAE) is defined as an adverse event that resulted in death, was life threatening, resulted in persistent or significant disability or incapacity, resulted in or prolonged a hospitalization, is a congenital anomaly or birth defect, is a cancer, was an overdose, or was an important medical event based on appropriate medical judgment. The percentage of participants with one or more SAE was assessed.
The VZV ELISPOT assay detects IFN-γ-secreting, VZV-specific cells from peripheral blood mononuclear cells (PBMCs). The unit of measure of the assay is ELISPOT cell count / 10\^6 PBMCs, and is expressed as geometric mean count (GMC). The GMFR is GMC at \~28 days after Vaccination 4 / GMC on Day 1.
An adverse experience (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the product is also an adverse experience. The percentage of participants with any AE was summarized.
An adverse experience (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the product is also an adverse experience. The percentage of participants with any injection-site AE was summarized.
An adverse experience (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the product is also an adverse experience. The percentage of participants with any systemic AE was summarized.
A serious AE (SAE) is an AE that results in death, is life threatening, results in persistent or significant disability or incapacity, results in or prolongs an inpatient hospitalization, is a congenital anomaly or birth defect, is an overdose, is a cancer, or is another important medical event. The percentage of participants with any SAE that was deemed by the investigator to be possibly, probably, or definitely related to study vaccine was summarized.
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the product is also an adverse experience. The percentage of participants with study vaccine withdrawn due to an AE was summarized.
Participants were given the VZV skin test prior to vaccination. For the baseline VZV skin test, they were administered VZV skin test reagent and saline in opposite arms, and assessed for a skin reaction around the injection site. The skin reaction assessed was erythema (redness of skin) and induration (palpable, raised, hardened area) around the injection site, which was marked with a ball point pen. The longest dimension to the closest 1 mm was measured. Participants with a reaction measure \< 5mm for saline and \< 5mm for the VZV antigen were considered to have a negative baseline skin test.
Number of participants with a positive VZV skin test after 2 vaccine doses was determined. Participants with a negative VZV skin test reaction at baseline were evaluated for VZV immunogenicity by a final VZV skin test administered 14 days after dose 2 of vaccination. For the VZV skin test participants were injected intradermally with the VZV skin test reagent, and reaction to the skin test was assessed after 48-72 hrs. A skin reaction (erythema and induration) around the injection site measuring \>= 5mm for the VZV antigen was considered a positive skin test.
Serum samples were tested for antibody response using a glycoprotein enzyme-linked immunosorbent assay (gpELISA) in gamma-irradiated VZV vaccine A recipients. The geometric mean fold rise (GMFR) is the response at approximately 28 days postdose 4 / response predose on Day 1. This outcome measure applied only to participants who received VZV vaccine A; heat-treated VZV vaccine and placebo participants were not assessed for this outcome.
Serum samples were tested for antibody response using gpELISA in gamma-irradiated VZV vaccine B recipients. The GMFR is the response at approximately 28 days postdose 4 / response predose on Day 1.
Serum samples were tested for antibody response using gpELISA in gamma-irradiated VZV vaccine C recipients. The GMFR is the response at approximately 28 days postdose 4 / response predose on Day 1.
An adverse event (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the study vaccine. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. Vaccination Report Card (VRC)-prompted injection-site AEs included redness, swelling, and pain/tenderness/soreness. The percentage of participants with one or more VRC prompted injection-site AE was assessed with incidence \> 0% in one or more vaccination groups.
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the study vaccine. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. VRC-prompted systemic AEs included non-injection-site varicella-like and herpes zoster (HZ)-like rashes. The percentage of participants with one or more VRC-prompted systemic AE was assessed with incidence \> 0% in one or more vaccination groups.
Elevated temperature is defined as ≥100.5 °F (≥38.1 °C), oral equivalent. The percentage of participants with VRC-prompted elevated temperature was assessed.
An adverse event (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the study vaccine. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. The percentage of participants who discontinued the study drug due to one or more AEs was assessed.
Blood sample taken at predose (Day 1) and 28 days post vaccination 4 to determine the geometric mean titre (GMT) of VZV antibodies via ELISPOT. The GMFR was calculated as GMT Post-dose/GMT Pre-vaccination
An SAE was defined as an adverse event that resulted in death, was life threatening, resulted in persistent or significant disability or incapacity, resulted in or prolonged a hospitalization, is a congenital anomaly or birth defect, is a cancer, was an overdose, or was an important medical event based on appropriate medical judgment. The percentage of participants that experienced at least 1 SAE was summarized.
| Arm | Type | Description |
|---|---|---|
| V212-STM | EXPERIMENTAL | Participants with STM receiving chemotherapy randomized to receive V212 vaccine given as a 4-dose regimen administered \~30 days apart. |
| V212-HM | EXPERIMENTAL | Participants with HM randomized to receive V212 vaccine given as a 4-dose regimen administered \~30 days apart. |
| Placebo-STM | PLACEBO_COMPARATOR | Participants with STM receiving chemotherapy randomized to receive placebo to V212 vaccine given as a 4-dose regimen administered \~30 days apart. |
| Placebo-HM | PLACEBO_COMPARATOR | Participants with HM randomized to receive placebo to V212 vaccine given as a 4-dose regimen administered \~30 days apart. |
| V212 Consistency Lot 1 | EXPERIMENTAL | Participants randomized to receive V212 consistency Lot 1 given as a 0.5 mL subcutaneous injection at 30 days before and 30, 60, and 90 days after auto-HCT. |
| V212 Consistency Lot 2 | EXPERIMENTAL | Participants randomized to receive V212 consistency Lot 2 given as a 0.5 mL subcutaneous injection at 30 days before and 30, 60, and 90 days after auto-HCT. |
| V212 Consistency Lot 3 | EXPERIMENTAL | Participants randomized to receive V212 consistency Lot 3 given as a 0.5 mL subcutaneous injection at 30 days before and 30, 60, and 90 days after auto-HCT. |
| V212 High Antigen Lot | EXPERIMENTAL | Participants randomized to receive V212 High Antigen Lot given as a 0.5 mL subcutaneous injection at 30 days before and 30, 60, and 90 days after auto-HCT. |
| Placebo | PLACEBO_COMPARATOR | Participants randomized to receive matching placebo given as a 0.5 mL subcutaneous injection at 30 days before and 30, 60, and 90 days after auto-HCT. |
| V212 | EXPERIMENTAL | Participants receive V212 as a 0.5 mL subcutaneous injection in a four-dose regimen, approximately 30 days apart, preferably in the deltoid area of the arm, alternating arms for each dose. |
| Zostavax™ | ACTIVE_COMPARATOR | Participants randomized to receive Zostavax™ (Zoster Vaccine, live) |
| Part 1: Heat-treated Varicella-Zoster Virus (VZV) Vaccine | EXPERIMENTAL | Participants received an 0.65 mL subcutaneous injection of heat-treated varicella zoster virus (VZV) vaccine A; 4-dose regimen administered \~30 days apart. |
| Part 1: Gamma- Irradiated VZV Vaccine A | EXPERIMENTAL | Participants received an 0.65 mL subcutaneous injection of alternative inactivation method VZV vaccine A; 4-dose regimen administered \~30 days apart. |
| Part 1: Placebo | PLACEBO_COMPARATOR | Participants received a 4-dose placebo regimen administered \~30 days apart. |
| Part 2: Gamma- Irradiated VZV Vaccine B | EXPERIMENTAL | Participants received an 0.65 mL subcutaneous injection of alternative inactivation method VZV vaccine B; 4-dose regimen administered \~30 days apart. |
| Part 2: Gamma- Irradiated VZV Vaccine C | EXPERIMENTAL | Participants received an 0.65 mL subcutaneous injection of alternative inactivation method VZV vaccine C; 4-dose regimen administered \~30 days apart. |
| Autologous HCT-V212 | EXPERIMENTAL | Participants receive V212 as a 0.65 mL subcutaneous injection in a four-dose regimen, approximately 30 days apart, preferably in the deltoid area of the arm, alternating arms for each dose. |
| Autologous HCT-Placebo | PLACEBO_COMPARATOR | Participants receive placebo as a 0.65 mL subcutaneous injection in a four-dose regimen, approximately 30 days apart, preferably in the deltoid area of the arm, alternating arms for each dose. |
| Allogeneic HCT-V212 | EXPERIMENTAL | Participants receive V212 as a 0.65 mL subcutaneous injection in a four-dose regimen, approximately 30 days apart, preferably in the deltoid area of the arm, alternating arms for each dose. |
| Allogeneic HCT-Placebo | PLACEBO_COMPARATOR | Participants receive placebo as a 0.65 mL subcutaneous injection in a four-dose regimen, approximately 30 days apart, preferably in the deltoid area of the arm, alternating arms for each dose. |
| STM-V212 | EXPERIMENTAL | Participants receive V212 as a 0.65 mL subcutaneous injection in a four-dose regimen, approximately 30 days apart, preferably in the deltoid area of the arm, alternating arms for each dose. |
| STM-Placebo | PLACEBO_COMPARATOR | Participants receive placebo as a 0.65 mL subcutaneous injection in a four-dose regimen, approximately 30 days apart, preferably in the deltoid area of the arm, alternating arms for each dose. |
| HM-V212 | EXPERIMENTAL | Participants receive V212 as a 0.65 mL subcutaneous injection in a four-dose regimen, approximately 30 days apart, preferably in the deltoid area of the arm, alternating arms for each dose. |
| HM-Placebo | PLACEBO_COMPARATOR | Participants receive placebo as a 0.65 mL subcutaneous injection in a four-dose regimen, approximately 30 days apart, preferably in the deltoid area of the arm, alternating arms for each dose. |
| HIV-V212 | EXPERIMENTAL | Participants receive V212 as a 0.65 mL subcutaneous injection in a four-dose regimen, approximately 30 days apart, preferably in the deltoid area of the arm, alternating arms for each dose. |
| HIV-Placebo | PLACEBO_COMPARATOR | Participants receive placebo as a 0.65 mL subcutaneous injection in a four-dose regimen, approximately 30 days apart, preferably in the deltoid area of the arm, alternating arms for each dose. |
| Name | Type | Description |
|---|---|---|
| V212 | BIOLOGICAL | V212 viral antigen for HZ, 0.5 mL subcutaneous (SC) injection per dose, in a four dose regimen, approximately 30 days apart. |
| Placebo | BIOLOGICAL | Vaccine stabilizer for V212 with no virus antigen, 0.5 mL SC injection per dose, in a four dose regimen, approximately 30 days apart. |
| Matching placebo | BIOLOGICAL | Vaccine stabilizer for V212 with no virus antigen |
| Comparator: Zostavax™ | BIOLOGICAL | Two doses of 0.65 mL Zostavax™ subcutaneous injection administered at Day 1 and Day 31 |
| Comparator: Placebo | BIOLOGICAL | Two doses of 0.65 mL subcutaneous injection of placebo administered at Day 1 and Day 31 |
| VZV Skin Test | OTHER | Three intradermal injections of the 0.1 ml varicella antigen (VZV Skin Test reagent) were administered, once at baseline before the first vaccination, a second time before the second vaccination, and a third time approximately 14 days after the second vaccination. |
| Saline | OTHER | One intradermal injection of the 0.1 ml saline was administered at the time of the baseline VZV skin test prior to the first vaccination. Saline and VZV skin test reagents were administered on opposite arms. |
| Comparator: V212 | BIOLOGICAL | 0.65 mL subcutaneous injection of heat-treated Varicella zoster virus (VZV) vaccine or alternative inactivation method VZV vaccine A, B, C; 4-dose regimen administered \~30 days apart |
Inclusion criteria: * Has been diagnosed with an STM or HM and is not likely to undergo hematopoietic cell transplant (HCT) and is either ≥18 years of age and receiving a cytotoxic or immunosuppressive chemotherapy regimen OR is ≥ 50 years of age with a hematologic malignancy that is not in remissi...